Migraine headaches affect 12% of the American population, incur $13 billion in annual direct and indirect costs, and cause the majority of the five million annual headache visits to American emergency departments (ED). In the American population, migraines are under-diagnosed and under-treated, particularly in lower socio-economic groups. Because an ED visit may be the migraine sufferer's first and only point of contact with the health care system, it represents an opportunity not only to treat a specific attack, but to engage the headache sufferer in an appropriate treatment program. Dr. Friedman will use the Award period to develop a foundation for a career focused on the ED diagnosis and treatment of headaches. Specifically, he will identify problematic areas in the ED management of migraines, determine who is at risk of poor outcomes after an ED visit for migraine, and conduct clinical trials to help define the optimal ED treatment of this disease. Eventually, this work will inform the development of evidence-based practice guidelines for the ED management of acute migraine headaches. Dr. Friedman will first conduct an observational cohort study in two EDs in the Bronx, NY. This study will classify all ED patients with non-traumatic headache and follow them for three months after their ED visit to determine if the presence of cutaneous allodynia or a high baseline disability score predicts poor pain and disability outcomes after ED discharge. Dr. Friedman will then conduct a clinical trial in the same two EDs to compare the efficacy of intramuscular trimethobenzamide to sumatriptan for acute migraine headaches. Trimethobenzamide has demonstrated good efficacy for acute migraines in preliminary data. In the latter years of the Award, the applicant will recruit other investigators and form an ED-based headache research network to conduct a series of headache trials in a standardized manner. The first clinical trial conducted by this research network will test the hypothesis that migraine sufferers treated with parenteral corticosteroids in addition to the standard of care will become headache pain-free more rapidly after ED treatment than those patients treated with placebo plus standard of care. By the end of the Award period, Dr. Friedman will apply for independent funding to use this ED-based research network to develop and validate comprehensive headache guidelines to optimize ED diagnosis and treatment of acute migraines and other primary headache disorders.